A total synthesis of (−)-hortonone C

Abstract

A total synthesis of the cytotoxic terpenoid hortonone C was accomplished and its absolute stereochemistry confirmed. Intermediate (+)-4 was synthesized using either an asymmetric conjugate addition strategy, or by elaboration of the Hajos-Parrish ketone. Reduction of (+)-4 under dissolving-metal conditions and trapping the enolate intermediate served to control the cis-stereochemistry at the ring fusion and provide a silyl enol ether necessary for ring expansion. Comparison of optical rotation data confirmed that the absolute configuration of natural hortonone C is (6S,7S,10S).

Design, synthesis, and evaluation of cystargolide-based β-lactones as potent proteasome inhibitors

“…As a continuation of our interest in optimizing the anticancer activity of natural products [22, 25], and desiring to discover PIs with novel modes of action [26], we designed and synthesized an array of analogs based on 1 to develop comprehensive SAR for the cystargolide scaffold. Structural modification focused on three major components of the scaffold (Scheme 1b): substitution at the β-lactone side chain (P 1 ), the composition of the internal dipeptide (P X and P y ), and the functionality of the acid derivative cap at the end of our scaffold (P z ).…”

Small rings in the bigger picture: ring expansion of three- and four-membered rings to access larger all-carbon cyclic systems

“…20 It relies on the well-known Saegusa one-carbon ring expansion protocol 21 of [4.1.0] bicyclic structures (Scheme 5). Accordingly, the corresponding sevenmembered ring found in the intricated unusual structure of echinopine B (13) 22 and the cytotoxic terpenoid (À)-hortonone C ( 14) 23 was satisfyingly delivered thanks to this approach. Parented examples were also described in the literature and allowed the total synthesis of (AE)-schindilactone A ( 15) 24 (eqn (1)) and rameswaralide (16) (eqn ( 2)) (Scheme 6).…”